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anest
4/30/98

perkowski

Pain management in 
small animals:

the first thing you have to do when you want to treat 
pain in veterinary patients is to acknowledge that the patients feel 
pain, and deserve to have it treated. many people in the veterinary 
community have taken a long time to recognize tht animals do feel pain 
like we do, but they do not show it the same way we do. This makes 
evolutionary sense though - an animal that shows signs of pain will be an 
easy target for predators, or be challenged in dominance matches.


animals do have pain pathways and do feel pain.

assessing pain is 
difficult - we rely a lot on the owners, and it takes a lot of experience 
to figure out if the animal is painful or not. 
treatment is hard - many 
spp with many drug tolerance differences
reassessment is also important 
and difficult

part of the problem with pain is that it is, by 
definition, subjective.
the IASP calls it "an unpleasant sensory and 
emotional experience associated with actual or potential tissue 
damage..."

sometimes you look at a patient and it is obviously in pain - 
dog with porcupine quills all over face. sometimes it isn't obvious. we 
need to assess patients for pain, then figure out how to treat it.

for 
many years, vets often said "pain is good, has benefits:"
produce 
immobility - good to make patient rest postop.
encourages rest, healing, 
recuperation.
to a small extent this is true, but negative aspects 
outweigh benefits:
immobility can lead to muscle atrophy, decrease rate 
of healing
prolonged recumbency promotes pneumonia, poor ventilation

decreased pulmonary function in ill patients, esp post thoracotomy
there 
are autonomic nervous system changes like catecholamine release that 
occur
stress hormones like cortisol, acth are released and are catabolic

behavioral changes - insomnia, inappetance
also, the patient suffers! we 
care about animals. we do not want them to suffer. there are other ways 
to produce the beneficial type of immobility. it doesn't have to be pain.


Pain is subjective, but it is closely related to nociception - which is a 
series of electrochemical events which occur and which lead to perception 
of pain.

nociception = four processes, measurable thigns.

transduction 
of stimulus by primary afferent nociceptor
transmission along nerve to 
dorsal horn of cord 
modulation by interneurons, descending info

transmision to thalamus, somatosensory cortex
integration with unique 
psyche of individual, production of pain sensation

1. transduction: when 
we discuss this, we mean what is happening in primary afferent 
nociceptors, found in cutaneous beds, muscles and joints (deep somatic), 
and viscera. they can be small myelinated Ad fibers with small receptive 
fields that conduct quickly, or unmyelinated C fibers that have large 
receptive fields. the first pain you feel is medited by Ad receptors, 
diffuse afterpain is from C fibers. there are also larger myelinated Aa 
fibers whichconduct non noxious info really rapidly

in skin, they 
respond to mechanical and thermal stimuli. the C fibers in skin are 
polymodal, respond to mechanical, thermal and chemical stimuli
in deep 
somatic area - respond to mechanical and chemical stimuli in noxious 
range.
in viscera - respond to inflammatory change (chemical)(polymodal 
fibers); respond to mechanical stimuli - twisting, stretching, 
distension.

once transduction occurs, impulse is transmitted to cell 
body in DRG and to dorsal horn of cord, synapsing in laminae I, II 
(substantia gelatinosa, lots of modulation here), and V (relay station 
for rostral transmission). 

postulated NTs in dorsal horn:
message comes 
in through A or Cpolymodal fibers...then may release glutamate, substance 
P, cGRP, VIP, somatostatin, tachykinins, all have been postulated as 
important NTs. remember the first three.


from dorsal horn there are 
rostral projections - spinothalamic and spinoreticular tract important. 
the neospinothalamic tract is fairly monosynaptic, runs to thalamus and 
then projects to somatosensory cortex. very important for localization 
and characterization of nociceptive stimuli. the medial spinothalamic and 
spinoreticular tracts are polysynaptic, go to brainstem, hypothalamus, 
diffuse projectsion to forebrain, cortex. important for arousal 
mechanisms that occur with pain - cause release of stress hormones, 
catecholamines, general excitation of animal in response to pain.

from 
there, there are descending inputs from cortex through periventricular 
grey, hypothalamus, ,rostroventral medulla,through dorsoventral pons back 
to cord - depending where you are, different NTs are involved in the 
descending inhibitory pathways. brain says "ok, already - calm down" and 
sends down inhibitory messages. in dorsolat pons - NE is important. in 
rostroventral medulla serotonin is important. these are tied into opioid 
pathways too. there are at least three types of NTs important in these 
pathways.

back in cord, serotonin and NE important in dorsal horn. 
enkephalins - use delta receptor - also important. GABA and glycine also 
important in cord.
so knowing what you know, what can you do to control 
pain?

first, transduction of the message - can we inhibit this? can we 
give something locally? Sure. we can give local anesthetics - regional 
nerve blocks. these block transduction and transmission. also can give 
local anesthetic at cord level, epidurally or spinally - or we can give 
epidural opioids, to increase the inhibitory effect. we can give systemic 
opioids which work at the level of the cortex and the cord. we can give 
alpha2 agonists - xylazine, medetomidine - great visceral analgesics - 
the problem is the CV side effects they cause. if we think about it and 
about NE - we can give A2 agonist at the level of the dorsal horn, and 
decrease systemic dose. so you can give drugs differentially at different 
levels, directly where they have their primary effect.

it isn't a static 
system. what if you make an incision? you cause tissue damage, K+ and H+ 
and prostaglandins and bradykinins are released, stimulating primary 
afferent nociceptor, sensitizing it so it responds more, also the 
nociceptor can release substance P causing more bradykinin release - 
which causes more substance P release. when you eat a hot pepper - 
peppers contain capsaicin, which causes degranulation peripherally, and 
release of substance P, hwich causes that burning feeling in your mouth. 
also nociceptors can affect various infiltrating inflammatory cells, 
cause release of other pain inducing substances, leading to vasodilation, 
extravasation of protein, etc. inflammatory cells release mediators like 
histamine, etc - stimulate nociceptors adjacent to the area of injury. 


finally we get a wind up of these reflex sympathetic arcs - trauma 
happens, things are released, message goes to cord, then efferent 
sympathetic messages go back to site of pain, etc.

peripheral 
sensitization isn't all - also central. when we make an incision, and 
nociceptor fires repeatedly, it sensitizes dorsal horn neuron, which 
fires a lot to the brain, sends big message, this is WIND UP - a decrease 
in response threshold, increase in responsiveness once threshold is 
reached, increase in receptive field, and afterdischarge. modulated by 
NMDA receptor -and ketamine is an NMDA receptor (glutamate)_ antagonist - 
so ketamine may be good for preemptive analgesia - to prevent windup 
phenomenon of central sensitization from occuring. epidural local 
anesthetics are helpful, systemic or epidural opioids are also useful.  


also upregulation of some genes over time makes patients more susceptible 
to pain. baby boys that were circumcised vs not were studied and they 
found some things leading to changes in protocosl (now, analgesia is 
given). five years later, boys circumcised with no analgesics had lower 
pain thresholds than those that had been. so there are changes that can 
set patient up for more pain years down the line. this is important wrt 
tail docking etc when you have young patients undergoing surgery. if you 
do something without providing analgesia you may set it up for a lower 
pain threshold later.

windup thing lasts for 3 weeks postop!

how do we 
provide analgesia? first, you have to get to know your patient, know 
idiosyncracies of patient. learn to anticipate - what is underlying 
problem? some diseases like pancreatitis are always very painful. has 
surgery been performed? what kind? some are high pain procedures. was 
there a lot of tissue trauma involved? as a corrolary, how experienced 
was the surgeon? more experience == less tissue trauma.

intercostal 
thoracotomy - very painful! lots of tissue trauma, incision of many 
muscle bellies. remember - pulmonary function is compromised in these 
patients b/c you have done a thoracotomy. you want them to be breathing 
well so they do not hypoventilate or get pneumonia.

ophthalmalogic 
procedures - very painful. 
ears - ablations, etc - very painful postop.

orthopedic procedures, esp proximal joint procedures - more painful than 
distal joints,
amputations - very very painful - involves a lot of nerve 
severing. patients get phantom limb pain - person with limb amputated may 
have pain in, say, right thumb, due to sensitization of nerves proximal 
to site of amputation.

tissue trauma - dog run over by lawn mower. lots 
of superficial trauma - disruption of a lot of skin is very painful.


horse that ha a longbone fracture, recovered in pool - remember with 
horses, when they wake up, if they are really painful they will thrash a 
lot and can hurt themselves or their caretakers. worry about pain and 
what further damage they can cause if they are painful.

anticipate - if 
patient already has drugs on board - what kind? when were they given? 
what about individual variations - young and old patients are often less 
tolerant of pain than average adult. 

clinical signs of pain: what do we 
look for?

- physiologic signs:
increased HR, RR, Temp, BP, salivation

dilated pupiles, hyperglycemia
these are also signs of stress, anxiety

-other signs:
in dogs, people tend to focus on vocalization - but dogs 
vocalize for many reasons depending on the dog - moon is out, stranger is 
near, dog is near other dogs - this is often nonspecific. esp in postop 
period, patients will vocalize due to drugs, whatever. some spp do not 
vocalize - cats, horses, cows. 
restlessness, agitation - patients waking 
up from anesthesia may be very excited, too. you have to try to figure 
out is it dysphoria from drugs or is one area bothering them. dog may 
keep looking at surgical site. dog may not be able to lie down and go to 
sleep. often big dominant dogs, with GDV - are literally falling asleep 
on their feet. 
inappetance
aggression
"prayer position" to keep weight 
off the abdomen - sign of abdominal pain
licking/chewing of surgical 
site. itching kind of a low grade form of pain.
facial expression - hard 
to assess sometimes.
cats - often just sit in the back of the cage and 
not move, not groom, not eat = people call this depression but it is also 
possibly due to pain. people miss this. ruminants too - may just go off 
feed.
ruminants may also grind teeth as will foals if painful. 
horses 
may roll on the ground with abdominal pain, or may paw at floor, or 
stretch out. may sweat. 

so if we notice pain in a patient..then we have 
to treat them. what with? 

depends on the patient. what's wrong with it?


-opioids - used most frequently here in the small animal, to provide 
analgesia. 
they provide CV stability (except demerol, morphine 
-->histamine)
they are good analgesics and are reversible
downside: cause 
sedation (may be good sometimes), dysphoria (worse in some spp), 
respiratory depression (big concern with critical cases, thoracotomy 
cases, brachycephalics, head trauma patients), and vomiting (bad post 
abdominal surgery)

cats - opioids are used, but can cause excitation. 

horses- can use opioids but will get excited, may need something else
can 
try butorphanol - works great in cats, well in horses.
buprenorphine - 
partial mu agonist
the problem with these drugs is that analgesia is less 
pronounced - that's your tradeoff for fewer side effects.
another nice 
thing about butorphanol is it gives good visceral analgesia - horses with 
abdominal pain from distension, twisting - can have good relief from 
butorphanol.
if really worried about respiratory depression - try non 
systemic opioids.

epidural opioids:
morphine - preservative free - 1 
mg/ml
0.1 mg/kg (dogs) dilute to 0.2 ml/kg (??) with saline or with 0.5% 
bupivicaine

intraarticular opioids:
chronically painful joints have an 
upregulation of opioid receptors in the joints. can try using morphine, 
preservative free.

other analgesics:

local anesthetics:
we tend to use 
bupivicaine and lidocaine most often in small animals. bupivicaine is 
really long lasting so not used as much in lg animals. may use 
mepivicaine more in horses. these drugs work by blocking sodium channels. 
when AP is transmitted along nerve, it follows wave of depolarization 
driven by sodium influx. if you block the sodium channels, wave goes 
nowhere, AP doesn't go anywhere. 
methods of delivery
-local infiltration 
(line block for c-section, paravertebral blocks, etc)
-regional nerve 
block
-intercostal/interpleural nerve block
-intraarticular
-epidural



problems with locals - they do not block only sensory fibers, they also 
block others. the bigger the fiber, the less block - but sympathetic 
fibers are smaller than sensory fibers. if you give an epidural, you 
create sympathetic block (vasodilation, hypotension can occur) along with 
the sensory block. also, therapeutic doses of these drugs are close to 
toxic doses.
signs of toxicity- msucle twitches, CNS excitement early on, 
then convulsions, then coma, then respiratory arrest, cardiovascular 
arrest. if patient arrests due to overdose of say bupivicaine, you won't 
be able to bring it back.

NSAIDs - little pug dog with front leg 
musculoskeletal problem - good drug to use. these drugs, remember, 
inhibit the action of COX, so that arachadonic acid isn't converted to 
thromboxane, prostacyclin, or prostaglandins (cause vasodilation - 
redness, swelling; sensitization of peripheral pain receptors; are second 
messengers at dorsal horn). NSAIDs inhibit COX1 (constitutive) and COX2 
(induced during inflammation) but we are looking for specific COX2 
inhibitors to preserve normal function.
thromboxane A2 induces platelet 
aggregation so NSAID can inhibit clotting
prostaglandins are required for 
good normal renal blood flow - they cause renal vasodilation (and other 
vasodilation)
also important for hepatic and GI integrity, mucosal blood 
flow, increase bicarb secretion, mucous production, etc. important for GI 
mucosal barrier.

aspirin, banamine (flunxin meglumine - often in horses 
with colic, not small animals due to kidney and gi effects, feldene 
(piroxicam - used in orthopedic sx), phenylbutazone, ketoprofen, 
carprofen (rimadyl - supposed to be specific cox2 inhibitor - can cause 
GI ulcers, hepatopathy (other NSAIDs can too)

NOT naproxen (Aleve) - 
never give to dogs. one dose can cause perforated GI ulcers.

a2 
agonists, ketamine, steroids also can be used.
steroids block 
phospholipase 
always consider route of administration, dose - and give 
BEFORE you need it, not after you need it. always reevaluate. switch 
drugs if needed. be flexible. avoid "as needed."

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soma


yesterday, we were talking about how to calculate alveolar ventilation - 
he forgot something in the equation - 
barometric pressure, subtract out 
water vapor, multiply by o2 concentration - and you have to subtract CO2.


how to estimate alveolar concentration of O2

PA = [(ATM - H20 vapor 
pressure) * %O2] - CO2

so on 100% O2 you end up with a Pa about 700 (?)

ATM is about 750 to 760; H20 is about 33
the Pa CO2 you subtract is the 
concentration in the arteries, from you blood gas, because it 
equilibrates with what's in the alveoli

so now you can calculate an A-a 
gradient - alveolar - arteriolar gradient.

last we were discussing 
question 2, the question we stopped at  is - what should the TV and RR 
be, and how do you establish this?

basic guidelines - the approx TV is 
50 mL/kg. that's a guideline.
approx RR anywhere from 10-12 bpm if body 
temp is normal (37). if temp is lower or higher, different RR (increase 
RR for fever, i think?)

so you control ventilation, then you measure


PaCO2 = 40 (normal)
PaO2 = 225
pH = 7.45
bicarb = 27
std bicarb = 27. 


explain changes in bicarb and std bicarb from awake state to anesth and 
from anest w/spontaneous vent to controlled vent. (note: we're talking 
VOC here)

previous blood gases - 

PaCO2 was 61
bicarb was 32
PaO2 was 
200

these changes are due to an increase in alveolar ventilation, which 
increases when you increase RR. your drop in bicarb from 32 to 27 is due 
to the decrease in carbon dioxide, which is normally in equilibrium with 
H+ and HCO3-. so, you had a pure respiratory acidosis at first. lowering 
the CO2 by increasing alveolar ventilation (by increasing resp rate) will 
then by definition cause a decrease in bicarbonate. 

if a metabolic 
mixed disturbance had existed, you would have had to interpret that based 
on standard bicarb. BE in this horse was 3, b/c standard bicarb was the 
same as actual bicarb, and normal bicarb is about 24, so +3 is what we 
had since it was 27, and that's a slight metabolic alkalosis but that's 
normal in horses.

what about the change in O2 tension? you have a mild 
shunt. you know you have a shunt b/c the O2 tension is just too low for 
breathing 100% O2. the increase to 225 occurred simply because you 
reduced your CO2 - this will cause a slight increase in oxygen tension.


if an animal has an extreme shunt, with CO2 70 and O2 100, and you drop 
your CO2 by increasing RR, you will have a rise in O2 tension. if you 
PEEP that animal and then are able to ventilate the lower alveoli, you 
will further increase the O2 tension, dependent on the amount of positive 
end expiratory pressure the animal can tolerate. 

simply put - if you 
understand what's happening, you will understand. great.
so in this 
horse...
ok, mean BP was 75 mmHg
CO was 25 L/min
HR was 38 bpm

during 
controlled vent, you went to 62, 25, and 38
why? positive pressure 
ventilation compresses veins, decreases venous return, decreases mean 
pressure, CO.

you can also measure end tidal halothane concentration - 
in this horse, O2 flow was 2 L/min. in a 500 kg horse, this is a low 
flow. if you had 2 L/min in a 50 kg GSD, that would be high flow. but for 
this horse, this is almost a closed system. this horse probably uses 
1.5-2 L/min. in a dog, this would almost be nonrebreathing system. 
so if 
asked about flows in an exam question, look at the weight of the animal - 
chihuahua or rhino? 

delivered concentration was 3.5% halothane. end 
tidal conc was about 1% w/spontaneous vent. after 10 min on PPV, it rose 
to 1.2% but you had not changed delivered concentration. what's up with 
that? well, there's reduced peripheral uptake of halothane because there 
is decreased CO, decreased distribution of halothane to tissues - so 
there is a temporary increase in alveolar concentration. also you 
increased alveolar ventilation (you know this, because the CO2 went down. 
if you ventilate the animal and the CO2 doesn't go down, that means you 
didn't increase alveolar ventilation. alveolar ventilation is directly 
related to increases/decreases in CO2 - not O2). with increased alveolar 
ventilation you have increased delivery of anesthetic agent. so delivery 
goes up, distribution goes down, you end up with increased alveolar 
concentration. so answer == delivery up, distribution down. that's all 
you have to say.

ok. any other questions on this one?

next.

case 3. 
you are trying a new inhalation agent in experimental horse. questane was 
used in dog and had VP 243, MAC 1, B:G 1.5 and B:T 2.5. to plan this, you 
must consider which vaporizer to use - halo, meto, or iso vaporizer? 
- 
to answer this, know vapor pressure of other agents and pick vaporizer 
for agent with VP closest to 243. that would be halothane. (or iso)

what 
exhaled concentration will produce adequate anesthesia for surgical 
intervention? well, MAC is 1, so what mac do you need? 1.3

horse is 
intubated, ready to go - what concentrations and flows do you start with 
in this 500 kg animal? start with a concentration of 5 (he would accept 
3, though) for rapid induction. based on this drugs' characteristic what 
would be duration of induction period, and how does it compare to 
halothane, slower or faster? 

to answer this, look at blood:gas 
coefficent of 1.5 - this is going to be faster than halothane, which has 
B:G 2.5. 

how do you calculate approximate brain concentration? roughly, 
you have B:G 1.5, so at equilibrium you have 1.5 gm/100 gm blood (Huh?) - 
1.5%/100 grams of tissue. the B:T is 2.5, so multiply 2.5 * amount in 
blood and that is what you have in the brain. he's not going to ask this, 
though. but, if B:T coefficient is 2.5, you have 2.5 times more drug in 
the brain at equilibrium.

if you have alveolar conc of 1, and B:G = 1.5, 
you have 1.5 in blood. B:T is 2.5 so you have 2.5 x 1.5 in tissue - so 
you use that as the brain concentration.

so when you do all the 
multiplication and look at halo, iso, and meto - they all reach similar 
conc in brain. metofane you start with low delivery and high solubility, 
halo you start with higher delivery and lower solubility - end up with 
the same thing.

B:T coefficients vary with tissue.

you proceed with 
induction and put horse on table - induce with thiopental
horse breathes 
spontaneously. you catheterize facial artery

BP 95
HR 32
RR 10
horse 
pupils show nystagmus
EKG normal

what stage/plane of anesthesia is this 
horse in and how do you know/what criteria do you use to figure it out?


this horse is in light anesthetic plane (based on presence of nystagmus 
and high BP. plus you just started induction, can't be that deep), stage 
III anesthesia.

5 min later - nystagmus gone
BP 45
HR 16
RR 4
EKG normal

TV 2 L
CRT slow

well, we started with 5% concentration of questane - 
that was apparently too much. we had a rapid induction, with 
cardiovascular depression, probably MAC and B:G turned out to be 
different in horse than in dog. we misjudged how fast this drug would 
work. 

are you very, moderately, or not at all concerned?
moderately.

but dr soma is highly concerned because this is a horse, not a puppy. it 
is easier to alter the CV status of a small animal than a large animal. 
BP 45 is below the level of adequate coronary perfusion. you can't do 
closed chest massage in a horse.

what do you do?
turn off anesthetic, 
flush out system with O2 flush, ventilate with 100% O2, increase fluid 
rate dramatically (easier to alter CV status in dog, but in this case it 
isn't b/c horse is so big), give pressor. in this case (if this were a 
smaller spp we could tough it out for a few minutes and maybe in this 
case you could too, but he isn't going to) we don't need epinephrine yet 
- maybe ephedrine, dobutamine. ephedrine would probably work really well, 
boost CO, push pressure up to a reasonable level. this isn't a desperate 
situation b/c you caught it so early in the induction of anesthesia, not 
an hour later. you just miscalculated the speed of induction, the potency 
of this drug in the horse. 

you want to figure out MAC - how?

anesthetize a bunch of horses. find the lowest concentration at which the 
animal does not feel pain. you have to use a large enough sample size to 
get reasonable data. in horse, we think mac in horse is probably lower 
than in dog. or, it could just be this horse. 

now, you stabilized the 
horse, you have the real mac figured out, and the horse is breathing 8 
bpm spontaneously, BP 75, HR 32, normal EKG, PaO2 125, PaCO2 65, pH 7.28, 
BE +2, bicarb 30. is PaO2 what you expected? if not, explain.

PaO2 is 
too low. You have a V/Q abnormality - a shunt. 
pH is 7.28 why? too much 
CO2 == acidosis
explain bicarb = 30 ? because of increased CO2.
BE +2 = 
normal in horse
change in actual bicarb is really simply due to elevation 
of CO2. 

how can you correct the problem? 
increase alveolar ventilation 
by increasing the respiratory rate. that will cause a decrease in CO2 and 
an increase on O2 a little. to really correct the O2, you would have to 
use PEEP. but you do not have to treat this level of decreased O2 b/c 
your Hb is still saturated.

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